The gram positive bacteria Group B Streptococcus (GBS) is one of the most important causes of life-threatening bacterial infection in newborn infants, pregnant women, the elderly and individuals with chronic illness. Other gram positive bacteria such as Streptococcus pyogenes (GBS), Streptococcus pneumoniae (Strep pneumo), and Staphylococcus aureus (Staph) are also implicated in significant morbidity and mortality worldwide.
Various streptococci express on their surface multifunctional proteins that mediate both bacterial adhesion and acquisition of immune system components, contributing to a successful colonization of host mucosal surfaces (Jarva et al., 2003; Talay, 2005). In particular, Streptococcus agalactiae (GBS) and Streptococcus pyogenes (GAS) express a number of functionally-related proteins, characterized by their capacity to bind both human immunoglobulins (Boyle, 1998) and fluid-phase complement regulators (Jarva et al., 2004; Lindahl et al., 2005). In GBS, receptors for IgA and/or IgG belong to the M protein family (Stenberg et al., 1992); M proteins interact with the type II Fc region of immunoglobulins outside their antigen-combining site (Cunningham, 2000).
In GBS, the Bac protein (beta antigen) binds with high affinity to the Fc part of human serum IgA (Bevanger, 1983; Johnson and Ferrieri, 1984; Lindahl et al., 1990; Russell-Jones et al., 1984) and to complement regulator Factor H (FH), which avoid C3b deposition on GBS surface (Areschoug et al., 2002). The binding site for IgA has been located to the N-terminal half of the protein, while the FH-binding region is at the C-terminal half of Bac (Areschoug et al., 2002; Jarva et al., 2002). Bac is structurally related to the pneumococcal Hic protein, and they bind FH in an analogous fashion (Janulczyk et al., 2000; Jarva et al., 2004).
On the other hand, GAS acquires FH by M proteins and Fba, which contributes to the bacterium's capacity to evade phagocytosis by polymorphonuclear cells (Horstmann et al., 1988; Pandiripally et al., 2002; Pandiripally et al., 2003). M-proteins also mediate acquisition of C4 binding protein (C4bp), an important regulator of complement classical pathway component C3 convertase (C4b2a) (Berggard et al., 2001; Blom et al., 2004). M protein binding to C4b has both decay accelerating activity and cofactor activity for C4b cleavage in an analogous fashion as FH in the alternative pathway (Carlsson et al., 2005; Perez-Caballero et al., 2004; Thern et al., 1995).
GAS and GBS also secrete the C5a peptidase, a multifunctional enzyme that inactivates human C5a (Jarva et al., 2003; Wexler et al., 1985) and binds fibronectin, which promotes bacterial invasion of epithelial cells (Beckmann et al., 2002; Cheng et al., 2002).
Serum resistance factors are thought to play a role in mechanisms these gram positive bacteria use to evade the host immune response. There is, therefore, a continuing need in the art for identification of novel serum resistance factors in gram positive bacteria which can be used to develop compositions for the prevention or treatment of bacterial infection.